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CYTOLOGY OF BONE LESIONS
PRESENTER – DR. PREETI
MODERATOR – DR. HEMALATHA A
 Classification of bone tumors
 Aspiration techniques
 Inflammatory conditions
 Osteoid forming lesions
 Cartilage forming tumors
 Giant cell containing lesions
 Cystic lesions of bone
 Small cell neoplasms of bone
 Bony lesions composed predominantly of spindle shaped cells.
 Secondary metastasis to bone
 Ancillary tecniques
 Syndromes associated with bone tumors
Classification
ORIGIN
 Primary
 Secondary – Breast , lung, prostate, kidney and thyroid
Classification (W.H.O.)
According to the age
According to location
Uses of fnac bone
 The procedure is less traumatic than either CNB or open biopsy
 Used safely in difficult sites such as vertebrae or pelvic bone
 Allows rapid triage with coordination of further investigations and planning of anticipated therapy
 Advantage of using CT GUIDED - needles can be directed to various parts of a large
heterogeneous mass for a more thorough and representative sampling
Clinical features
 H/ O pain , progressive swelling
 Fracture
 Discharging sinus
 Limping
 Restriction of the movements
Bimodal distribution
Sampling Technique
Complications of FNA of the Bone
 Pneumothorax following needling of tumors in the ribs
 Neurologic sequel to needling of lesions in the vertebrae
Normal structures seen on cytology
of bone
 Osteoblasts
 Osteoclasts
 Chondrocytes
 Cartilage
 Hematopoietic tissue
Osteoblasts
Osteoclasts
Cartilage
Bone marrow cells.
BONE LESIONS AND ITS
FEATURES ON CYTOLOGY
INFLAMMATORY LESIONS
Case - 1
 A 15 year old boy comes to the opd with h/o
swelling and redness just below the knee with
pain in the knee since 5 days and h/o fever
since 3 days.
 X – ray was taken and it showed - area of
periosteal proliferation surrounded by
successive layers of condensed cortical bone .
On cytology
Osteomyelitis
 KEY FEATURES
1. Abundant neutrophils , macrophages and necrotic bone (acute)
2. Granulomatous process with Epithelioid cell granulomas and Occasional giant cells of
Langerhans type
3. Tuberculous osteomyelitis is due to hematogenous spread from the lungs.
4. The most common sites are the vertebra followed by pelvic bones and the knee
 Differential diagnosis: Langerhans cell histiocytosis
OSTEOID PRODUCING
LESIONS
Fracture Callus
 It’s a Reactive osteoblastic proliferation
 misdiagnosed as malignant bone neoplasm, commonly osteosarcoma (OS).
 Reactive osteoblasts in callus may display considerable pleomorphism with anisokaryosis
and hyperchromatic nuclei with prominent nucleoli .
 Their chromatin pattern is quite regular, and the cytoplasmic “hof” is often visible in some
cells.
 Clinical and radiologic correlation is essential to distinguish fracture callus from OS.
Cytological features
 Fracture callus. (a and b)
 Clusters of reactive
osteoblasts with anisokaryosis
 Hyperchromatic nuclei
embedded in osteoid-like
matrix (MGG)
Case – 2
 A 22 year old man with history of dull aching
pain in the neck since 1year
 On NSAIDs
 X – Ray - shows a well-circumscribed
radiolucent lesion in the bony cortex, with a
thin shell of peripheral new bone separating it
from the surrounding soft tissue
Cytological features
Osteoblastoma
 Differential diagnosis: Osteosarcoma
 Cytological features
1. Smears are moderately cellular , with a bloody background.
2. There is large number of plasmacytoid cells with eccentric nuclei that appear to protrude
from the cell.
3. Osteoclastic giant cells with upto 20nuclei per cell are visible.
4. Spindle cell aggregates occur in which the cells show no significant nuclear atypia.
5. Fragments of pink osteoid surrounded by osteoblast- like cells seen.
6. Mitotic figures are rare to absent in smear preparations.
Differential diagnosis
Differential diagnosis
OSTEOID OSTEOMA OSTEOBLASTOMA AGGRESSIVE OSTEOBLASTOMA
< 1.5 CMS > 1.5 CMS > 4 CMS
M/C – Long bones of lower
extremity (femur neck) , rarely in
small bones of hands & feet
Axial skeleton (vertebrae ,sacrum
,craniofacial bones)
Teenage and young adults 2nd decade
M: F - 3 :1 M: F - 3 :1
Cytology not done Osteoblasts seen and No mitosis /
atypia on cytology
Epithelioid osteoblasts , nuclear
pleomorphism and occasional
mitosis.
Dull pain worse at night and
disappearce within 20 – 30 minutes.
Pain of varying intensity – 2 yrs
Case - 3
 A 15 year old boy with h/o weight loss and
slow growing mass in the left shoulder since
3 years
 X- ray – showing densely sclerotic lesion with
cloudy opacities and irregular , ill-defined
borders. Cortex destroyed. The arrow
pointing to codmans triangle.
Cytology
Osteosarcoma
 Osteosarcoma (OS) is a primary bone tumor composed of cells, which at least focally
produce osteoid
 80% to 90 % of cases of OS are of the conventional highly malignant type.
 Majority of them occur around the knee followed by the humerus and pelvic bones
 Presentations - bone mass, often with a soft tissue involvement and pain
Osteoblastic subtype
 ( a and b )
 Large, atypical tumor cells with round
to oval, irregular nuclei, a moderate
amount of cytoplasm,and large
macronucleoli (MGG).
 ( c ) Poorly cohesive clusters of
pleomorphic cells, some with atypical
mitoses and admixture of
osteoclasts(H&E).
 ( d ) Pleomorphic tumor cell
resembling osteoblast and a small
fragment of the bone.
 ( e ) Calcification seen in liquid-based
preparations (H&E; ThinPrep)
Cytologic features of osteosarcoma:
2. CHONDROBLASTIC SUBTYPE
 Myxoid background matrix (red; red violet in MGG)
 Fragments of hyaline cartilage
 Cartilage with atypical chondrocytes in lacunae
 Atypical mono- or binucleated chondroblasts
 Admixture of similar cell population as in osteoblastic osteosarcoma in variable
proportions
Chondroblastic osteosarcoma
 Large, atypical tumor cells( a ) adjacent
to the cartilaginous matrix or dispersed in
the myxoid and chondroid background
matrix
 ( b and c ), which is more abundant than
osteoid matrix. Note tumor cells
resembling osteoblasts and mitoses
(MGG).
 ( d ) Malignant cartilage with atypical
chondroblasts embedded in a chondroid
matrix (H&E)
Giant cell-rich osteosarcoma
 (a–c) Smears resembling giant
cell tumor but clearly
pleomorphic tumor cells consist
with highly malignant neoplasm
(H&E).
 (d) Positive alkaline
phosphatase staining in tumor
cells but negative staining in
the osteoclast-like giant cells
(alkaline phosphatase stain)
Fibroblastic Osteosarcoma
 (a) Clusters of moderately atypical spindle
cells embedded in osteoid-like matrix (MGG).
 Small cell osteosarcoma.
 (b) FNA smears.
 (c) Cell block.
 Small- to medium-sized tumor cells with
rounded nuclei and scanty cytoplasm
resembling Ewing sarcoma (H&E)
Parosteal Osteosarcoma
 a rare type of low-grade osteosarcoma
arising on the surface of the bone.
 Clusters of slightly atypical spindle cells
embedded in osteoid-like matrix (MGG).
CARTILAGINOUS TUMORS
Case – 4
 20 year old women with h/o of pain in the
left shoulder since 2 weeks on and off .
 X- ray showed well circumscribed
expansile osteolytic lesion situated in a
medullary location.
 Punctate calcification or popcorn
appearance
Cytology
Chondroma
 Are benign cartilaginous neoplasms occurring within the bone
 Involve small tubular bones of the hands and feet , femur and humerus.
 Cytologic features
 Cartilaginous fragments containing cells in lacunar spaces
 Cells with small regular nuclei
 Often slight cellular pleomorphism
 Focal nuclear atypia and pleomorphism should not be mistaken for signs of malignancy.
 Differential diagnosis – Grade I Chondrosarcoma
Case – 5
 A 15 YEAR old boy comes with a history of right
knee swelling since 1 week and pain since 6
months .
 X- ray showed – Oval, eccentric metaphyseal lesions
oriented parallel to the long axis of the bone , with
sharply defined margins with sclerotic and scalloped
borders displaying a lytic lesion.
Cytological features
Chondromyxoid fibroma
 2nd – 3rd decade..
 Chondromyxoid fibroma arises usually in the metaphyseal region of long tubular bones,
especially the tibia
 Cytological features:
 Myxoid background matrix
 Cartilaginous fragments (with chondroblast-like cells in lacunae)
 Dispersed or clustered stellate or spindle-shaped myofibroblastic cells
 Osteoclastic giant cells
 Differential diagnosis – Chondrosarcoma , Enchondroma and chondroblastoma.
Case – 6
 28 year old female with h/ o hard
swelling and pain in the lower end of
right leg since 2 weeks.
 X- ray showed – pedunculated lesion
growing over the surface of the bone
which is smoothly contoured bony stalk
continuous with adjacent cortex.
Cytological features
Osteochondroma
 Never sampled by FNAC as its radiologic appearances are diagnostic.
 Cytological features
1. Fragments o mature hyaline cartilage .The fragments have sharp borders and appear heavy bodied
with lacunar spaces.
2. Chondrocytes are seen best with PAP and H& E.
3. Cell blocks are useful in diagnosis.
 Differential diagnosis – Parosteal osteosarcoma.
Case – 7
 A15 year old child came to hospital with h/
o pain and swelling in the knee with his
parents complaining of limping of right leg
since 3 days.
 X – ray showed sharply demarcated round
to oval epiphyseal lesions crossing
metaphysis with a rim of sclerotic bone.
Chondroblastoma
 A rare, benign chondrogenic lesion
 M:F = 2:1
 80% of patients under 25 years of age
 Cytological features
1. Mononuclear chondroblasts
characterized by well defined
cytoplasm and round nuclei
2. Multinucleated osteoclast-like cell
3. Fragments of chondroid matrix
4. The nucleus is grooved
Case – 8
 70 year old man presented to OPD with
h/ o severe pain in left hip since 1 year
and more in the night.
 X – ray – showed radiolucent areas in
the left Iliac bone containing moderate
amount of calcification.
Chondrosarcoma
 GRADE I (WELL
DIFFERENTIATED)
 low cellularity
 fragments of hyaline cartilage
with lacunar spaces
containing neoplastic
chondrocytes.
 Binucleated chondrocytes
are present
 No mitotic figures seen.
 Little or no myxoid –
chondroid matrix present.
Chondrosarcoma
 GRADE II
 Low to moderate cellularity.
 Hyaline and myxoid –
chondroid matrix are
frequently abundant.
 Neoplastic cells lie singly in
small clusters , within lacunar
spaces and in small sheets.
 Occasinal small nucleoli .
Chondrosarcoma
 GRADE III
 Cellular smears with abundant
myxoid – chondroid stroma.
 Mitotic figures present
 Cells have single large cytoplasmic
vacuoles displacing the nucleus to
the periphery giving a signet- ring
appearance.
Mesenchymal chondrosarcoma
 Aspirate – is gelatinous and blood tinged.
 Cytological features
1. cellular , with rich myxoid chondroid background matrix.
2. Two cell populations – a small primitive appearing cells and cells showing chondrocytic
differentiation.
3. Focal necrosis and acute inflammation
4. The chondrocyte like cell population with moderate to abundant cytoplasm containing vacuoles.
5. The cells characterized by eccentric nuclei with coarsely granular chromatin and distinct
nucleoli.
 Differential diagnosis – Small round cell malignancies , Intraosseous
hemangiopericytoma.
Mesenchymal chondrosarcoma
 Clusters of small, round to oval tumor
cells with sparse cytoplasm and
irregular nuclei.
 Cells embedded in a blue-violet
collagenous matrix (MGG).
Clear cell chondrosarcoma
 Large epithelioid cells with abundant
finely vacuolated cytoplasm,
 a central or paracentral nucleus,
fragments of cartilage, and
 occasional osteoclast-like giant cells
(MGG)
GIANT CELL – CONTAINING
LESIONS
Case - 9
 35 year old woman with h/o slow
growing mass in left wrist since 1
year and pain since 4weeks.
 X – ray showed – well defined
osteolytic lesion with incomplete
surrounding sclerosis with
multiloculated appearance .
On Cytology
Giant cell tumor
 Cytological features
 Hypercellular yield with both cohesive cell clusters and single cells.
 Double-cell population: mononuclear spindle or round to ovoid cells and multinucleated
osteoclast-like giant cells.
 Mononuclear cells contain nuclei with open chromatin and prominent nucleoli.
 The size of mononuclear cell nuclei is comparable to that in the osteoclast-like giant cells.
 Classical pattern of smears includes giant cells attached to the periphery of clusters of
mononuclear cells.
 Absence of osteoid and cartilaginous matrix.
Differential diagnosis
 Aneurysmal bone cyst
 Brown tumor of hyperparathyroidism
 Reparative giant cell granuloma
 Osteoblastoma
 Giant cell-rich osteosarcoma
Aneurysmal bone cyst
 Multilocular, locally destructive lesion.
 Age - < 20yrs.
 Vertebral column, the craniofacial bones,
and metaphysis of long tubular bones.
 X- Ray - seen as osteolytic , expansile,
eccentric lesions in metaphysis.
ABC cytology
 Cytologic features
 Hemorrhagic aspirates
 Variable numbers of multinucleated giant
cells
 Variable presence of clusters of spindled
myofibroblastic cells
 Histiocytes and inflammatory cells
 Lack of significant cytologic atypia
Brown Tumor of Hyperparathyroidism
 X- Ray
 Lytic lesion with irregular sclerosed
cortex
 Differential diagnosis and problems
in diagnosis:
 Conventional giant cell tumor
 Aneurysmal bone cyst
 Reparative giant cell granuloma
Brown Tumor of
Hyperparathyroidism
 Cytologic features
 Dispersed spindle cells or small- to
medium-sized clusters of spindle
cells
 Osteoclast-like giant cells
 Hemosiderin-laden macrophages
Giant Cell Reparative Granuloma
 X- Ray – Osteolytic ,eccentric lesion in
the epiphysis without a sclerotic margin.
 May show a soap bubble appearance.
Giant Cell Reparative Granuloma
 Cytologic features:
 Sheets and clusters of spindle cells
 Multinucleated giant cells
 Osteoblasts
 Histiocytes
 ( a and b ) (MGG; H&E).
 ( c ) Cell block - (H&E)
VASCULAR LESIONS
 Hemangioma – only blood is aspirated.
 Strands of endothelial cells with spindled , bland nuclei may be found in smears .
 Also seen are hemosiderin containing macrophages , osteoblasts and fibroblasts.
Cystic lesions of bone
 Unicameral bone cyst
 Aneurysmal bone cyst
 Telangiectatic Osteosarcoma
 Intraosseous ganglion cyst
 Subchondral Osteoarthritic Bone cyst
 Intraosseous Epidermal cysts.
BONE LESIONS COMPOSED OF
SPINDLE – SHAPED CELLS
Adamantinoma of long bones
 2ND AND 6TH DECADE
 M: f – 1.3 : 2
 H/o dull aching pain with swelling.
 X- Ray
 Metaphysis / Diaphysis
 Tibia / Fibula
 Eccentric zone of lysis
 Osteolytic area is bubbly / honeycomb
On cytology
 Cellular smears with small clusters of cells
 Majority are spindle shaped, some are
round to oval.
 Distinct / absent cytoplasm
 Necrotic debris in the background.
Intraosseous desmoplastic fibroma
 3rd decade.
 Mandible , pelvic bones and femur.
 Swelling , tenderness and aching pain.
 X- ray – shows Lytic appearance with
sclerotic margin.
 Orthopantomograph well-defined
radiolucent lesion over the right
mandible
Cytology
 Spindle shaped cells in clusters .
 Collagen fiber debris
 Bland nucleus with fine chromatin and small indistinct nucleoli.
 No mitotic figures seen.
Small cell neoplasm of bone
Case- 10
 15 year old man with slow growing
mass in the left arm since 1 year with
redness and pain since 1 week.
 X- RAY showed illdefined ,
permeative ,destructive
intramedullary lesion .Onion skin
appearance.
Ewings sarcoma - cytology
 Cellular
 Neoplastic cells with uniform size and
round shape
 Bimodal population of – light & dark cells
 Light cells – open chromatin
 Dark cells – condensed chromatin
 Glycogen / rosette like structures present
 Scanty cytoplasm , appears as thin rim.
Non – hodgkins lymphoma
 Very rare
 > 40 yrs
 Male predominance
 X- ray
 Lytic appearance
 Permeative moth eaten pattern
 Cortex is lysed with extension into
surrounding soft tissue.
 Periosteal new bone formation – onion
skin peal appearance.
Cytology
 Monorphous population of large lymphoid cells showing nuclear enlargement.
 The background is dirty
 Contains characteristic lymphoglandular bodies.
 Atypical lymphocytes are 2- 3 times the size of small lymphocyte.
Langerhans cell histiocytosis
 5 – 15 YRS
 3:2
 Skull , jaw , humerus, rib , femur.
 Metaphysis or diaphysis.
 Benign.
 X- ray
 Lytic masses that may extend into soft
tissue
Cytology
 cellular with large, polygonal cells with ample
cytoplasm, nuclei are round, oval or bean
shaped with fine and even chromatin and
prominent longitudinal grooves
Inconspicuous nucleoli, mild pleomorphism
 No / minimal mitotic figures
 Scattered eosinophils and neutrophils and
multinucleated osteoclast-like giant cells
 Necrosis common
METASTATIC DISEASES
Breast carcinoma mets to bone
 usually appear in the medullary cavity,
spread to destroy the medullary bone, and
then involve the cortex
Cytology
 Metastatic ductal carcinoma of the breast
shows cells arranged in loose clusters.
Inset. Details of nuclear morphology with
coarse chromatin and prominent irregular
nucleoli.
Carcinoma prostate
 densely sclerotic osteoblastic metastases,
which frequently involve vertebral bodies and
the pelvis
 Metastatic foci can be obliterated by a
pronounced osteoblastic reaction
Cytology
 . A,B. Large cohesive sheets of prostatic
carcinoma cells.
 the nuclei of the tumor cells are uniform
in size with minimal atypia.
 prominent nucleoli, and evenly
distributed chromatin.
Carcinoma of lung
 O15 % of carcinomas metastases to bone
 Lytic lesions in bone
Cytology – mets of ca of lung
 Clusters of the large lung
adenocarcinoma cells showing
obvious cytologic atypia
Electron microscopy
 Diagnosis of Langerhans cell histiocytosis (Birbeck granule)
 Rare cases of osteosarcoma (osteoid)
Cytochemistry
 Alkaline phosphatase (ALP) – Osteoblastic differentiation
 Positive in Osteosarcoma
Ancillary uses
Algorithm of fnac of bony lesions
Syndromes associated with bone tumors
Reporting the diagnosis on bone
lesions
 Sarcoma (histologic type of sarcoma or sarcoma not otherwise specified [NOS])
 Benign tumor (histologic type or benign tumor NOS)
 Metastasis (suggestion of primary or descriptive diagnosis)
 Lymphohematologic malignancy (exact subtype defined or general classification as malignant
lymphoma, non-Hodgkin lymphoma)
 Non neoplastic lesion (infectious, reactive)
 Non diagnostic (including insufficient)
A standardized reporting of bone FNA has been suggested
by Åkerman et al.
To Summarize
 Age , Clinical features, Specific site, Radiology , Clinical presentation and underlying
conditions.
 FNA technique should be based on the location of the tumor.
 Algorithm approach helps in making a appropriate diagnosis.
References
 Cytopathology of bone and soft tissue tumors by Lester J Layfield
 Current concepts in Bone and soft tissue tumors by Dr.Ajay Puri
 Koss diagnostic cytology and its Histopathologic bases.
 Atlas of Fine needle aspiration cytology by Henryk . A . Domanski.
 Internet sources.
THANK YOU

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Cytology of bone lesions

  • 1. CYTOLOGY OF BONE LESIONS PRESENTER – DR. PREETI MODERATOR – DR. HEMALATHA A
  • 2.  Classification of bone tumors  Aspiration techniques  Inflammatory conditions  Osteoid forming lesions  Cartilage forming tumors  Giant cell containing lesions  Cystic lesions of bone  Small cell neoplasms of bone  Bony lesions composed predominantly of spindle shaped cells.  Secondary metastasis to bone  Ancillary tecniques  Syndromes associated with bone tumors
  • 3. Classification ORIGIN  Primary  Secondary – Breast , lung, prostate, kidney and thyroid
  • 7. Uses of fnac bone  The procedure is less traumatic than either CNB or open biopsy  Used safely in difficult sites such as vertebrae or pelvic bone  Allows rapid triage with coordination of further investigations and planning of anticipated therapy  Advantage of using CT GUIDED - needles can be directed to various parts of a large heterogeneous mass for a more thorough and representative sampling
  • 8. Clinical features  H/ O pain , progressive swelling  Fracture  Discharging sinus  Limping  Restriction of the movements
  • 11. Complications of FNA of the Bone  Pneumothorax following needling of tumors in the ribs  Neurologic sequel to needling of lesions in the vertebrae
  • 12. Normal structures seen on cytology of bone  Osteoblasts  Osteoclasts  Chondrocytes  Cartilage  Hematopoietic tissue
  • 17. BONE LESIONS AND ITS FEATURES ON CYTOLOGY
  • 19. Case - 1  A 15 year old boy comes to the opd with h/o swelling and redness just below the knee with pain in the knee since 5 days and h/o fever since 3 days.  X – ray was taken and it showed - area of periosteal proliferation surrounded by successive layers of condensed cortical bone .
  • 21. Osteomyelitis  KEY FEATURES 1. Abundant neutrophils , macrophages and necrotic bone (acute) 2. Granulomatous process with Epithelioid cell granulomas and Occasional giant cells of Langerhans type 3. Tuberculous osteomyelitis is due to hematogenous spread from the lungs. 4. The most common sites are the vertebra followed by pelvic bones and the knee  Differential diagnosis: Langerhans cell histiocytosis
  • 23. Fracture Callus  It’s a Reactive osteoblastic proliferation  misdiagnosed as malignant bone neoplasm, commonly osteosarcoma (OS).  Reactive osteoblasts in callus may display considerable pleomorphism with anisokaryosis and hyperchromatic nuclei with prominent nucleoli .  Their chromatin pattern is quite regular, and the cytoplasmic “hof” is often visible in some cells.  Clinical and radiologic correlation is essential to distinguish fracture callus from OS.
  • 24. Cytological features  Fracture callus. (a and b)  Clusters of reactive osteoblasts with anisokaryosis  Hyperchromatic nuclei embedded in osteoid-like matrix (MGG)
  • 25. Case – 2  A 22 year old man with history of dull aching pain in the neck since 1year  On NSAIDs  X – Ray - shows a well-circumscribed radiolucent lesion in the bony cortex, with a thin shell of peripheral new bone separating it from the surrounding soft tissue
  • 27. Osteoblastoma  Differential diagnosis: Osteosarcoma  Cytological features 1. Smears are moderately cellular , with a bloody background. 2. There is large number of plasmacytoid cells with eccentric nuclei that appear to protrude from the cell. 3. Osteoclastic giant cells with upto 20nuclei per cell are visible. 4. Spindle cell aggregates occur in which the cells show no significant nuclear atypia. 5. Fragments of pink osteoid surrounded by osteoblast- like cells seen. 6. Mitotic figures are rare to absent in smear preparations.
  • 29. Differential diagnosis OSTEOID OSTEOMA OSTEOBLASTOMA AGGRESSIVE OSTEOBLASTOMA < 1.5 CMS > 1.5 CMS > 4 CMS M/C – Long bones of lower extremity (femur neck) , rarely in small bones of hands & feet Axial skeleton (vertebrae ,sacrum ,craniofacial bones) Teenage and young adults 2nd decade M: F - 3 :1 M: F - 3 :1 Cytology not done Osteoblasts seen and No mitosis / atypia on cytology Epithelioid osteoblasts , nuclear pleomorphism and occasional mitosis. Dull pain worse at night and disappearce within 20 – 30 minutes. Pain of varying intensity – 2 yrs
  • 30. Case - 3  A 15 year old boy with h/o weight loss and slow growing mass in the left shoulder since 3 years  X- ray – showing densely sclerotic lesion with cloudy opacities and irregular , ill-defined borders. Cortex destroyed. The arrow pointing to codmans triangle.
  • 32. Osteosarcoma  Osteosarcoma (OS) is a primary bone tumor composed of cells, which at least focally produce osteoid  80% to 90 % of cases of OS are of the conventional highly malignant type.  Majority of them occur around the knee followed by the humerus and pelvic bones  Presentations - bone mass, often with a soft tissue involvement and pain
  • 33. Osteoblastic subtype  ( a and b )  Large, atypical tumor cells with round to oval, irregular nuclei, a moderate amount of cytoplasm,and large macronucleoli (MGG).  ( c ) Poorly cohesive clusters of pleomorphic cells, some with atypical mitoses and admixture of osteoclasts(H&E).  ( d ) Pleomorphic tumor cell resembling osteoblast and a small fragment of the bone.  ( e ) Calcification seen in liquid-based preparations (H&E; ThinPrep)
  • 34. Cytologic features of osteosarcoma: 2. CHONDROBLASTIC SUBTYPE  Myxoid background matrix (red; red violet in MGG)  Fragments of hyaline cartilage  Cartilage with atypical chondrocytes in lacunae  Atypical mono- or binucleated chondroblasts  Admixture of similar cell population as in osteoblastic osteosarcoma in variable proportions
  • 35. Chondroblastic osteosarcoma  Large, atypical tumor cells( a ) adjacent to the cartilaginous matrix or dispersed in the myxoid and chondroid background matrix  ( b and c ), which is more abundant than osteoid matrix. Note tumor cells resembling osteoblasts and mitoses (MGG).  ( d ) Malignant cartilage with atypical chondroblasts embedded in a chondroid matrix (H&E)
  • 36. Giant cell-rich osteosarcoma  (a–c) Smears resembling giant cell tumor but clearly pleomorphic tumor cells consist with highly malignant neoplasm (H&E).  (d) Positive alkaline phosphatase staining in tumor cells but negative staining in the osteoclast-like giant cells (alkaline phosphatase stain)
  • 37. Fibroblastic Osteosarcoma  (a) Clusters of moderately atypical spindle cells embedded in osteoid-like matrix (MGG).  Small cell osteosarcoma.  (b) FNA smears.  (c) Cell block.  Small- to medium-sized tumor cells with rounded nuclei and scanty cytoplasm resembling Ewing sarcoma (H&E)
  • 38. Parosteal Osteosarcoma  a rare type of low-grade osteosarcoma arising on the surface of the bone.  Clusters of slightly atypical spindle cells embedded in osteoid-like matrix (MGG).
  • 40. Case – 4  20 year old women with h/o of pain in the left shoulder since 2 weeks on and off .  X- ray showed well circumscribed expansile osteolytic lesion situated in a medullary location.  Punctate calcification or popcorn appearance
  • 42. Chondroma  Are benign cartilaginous neoplasms occurring within the bone  Involve small tubular bones of the hands and feet , femur and humerus.  Cytologic features  Cartilaginous fragments containing cells in lacunar spaces  Cells with small regular nuclei  Often slight cellular pleomorphism  Focal nuclear atypia and pleomorphism should not be mistaken for signs of malignancy.  Differential diagnosis – Grade I Chondrosarcoma
  • 43. Case – 5  A 15 YEAR old boy comes with a history of right knee swelling since 1 week and pain since 6 months .  X- ray showed – Oval, eccentric metaphyseal lesions oriented parallel to the long axis of the bone , with sharply defined margins with sclerotic and scalloped borders displaying a lytic lesion.
  • 45. Chondromyxoid fibroma  2nd – 3rd decade..  Chondromyxoid fibroma arises usually in the metaphyseal region of long tubular bones, especially the tibia  Cytological features:  Myxoid background matrix  Cartilaginous fragments (with chondroblast-like cells in lacunae)  Dispersed or clustered stellate or spindle-shaped myofibroblastic cells  Osteoclastic giant cells  Differential diagnosis – Chondrosarcoma , Enchondroma and chondroblastoma.
  • 46. Case – 6  28 year old female with h/ o hard swelling and pain in the lower end of right leg since 2 weeks.  X- ray showed – pedunculated lesion growing over the surface of the bone which is smoothly contoured bony stalk continuous with adjacent cortex.
  • 48. Osteochondroma  Never sampled by FNAC as its radiologic appearances are diagnostic.  Cytological features 1. Fragments o mature hyaline cartilage .The fragments have sharp borders and appear heavy bodied with lacunar spaces. 2. Chondrocytes are seen best with PAP and H& E. 3. Cell blocks are useful in diagnosis.  Differential diagnosis – Parosteal osteosarcoma.
  • 49. Case – 7  A15 year old child came to hospital with h/ o pain and swelling in the knee with his parents complaining of limping of right leg since 3 days.  X – ray showed sharply demarcated round to oval epiphyseal lesions crossing metaphysis with a rim of sclerotic bone.
  • 50. Chondroblastoma  A rare, benign chondrogenic lesion  M:F = 2:1  80% of patients under 25 years of age  Cytological features 1. Mononuclear chondroblasts characterized by well defined cytoplasm and round nuclei 2. Multinucleated osteoclast-like cell 3. Fragments of chondroid matrix 4. The nucleus is grooved
  • 51. Case – 8  70 year old man presented to OPD with h/ o severe pain in left hip since 1 year and more in the night.  X – ray – showed radiolucent areas in the left Iliac bone containing moderate amount of calcification.
  • 52. Chondrosarcoma  GRADE I (WELL DIFFERENTIATED)  low cellularity  fragments of hyaline cartilage with lacunar spaces containing neoplastic chondrocytes.  Binucleated chondrocytes are present  No mitotic figures seen.  Little or no myxoid – chondroid matrix present.
  • 53. Chondrosarcoma  GRADE II  Low to moderate cellularity.  Hyaline and myxoid – chondroid matrix are frequently abundant.  Neoplastic cells lie singly in small clusters , within lacunar spaces and in small sheets.  Occasinal small nucleoli .
  • 54. Chondrosarcoma  GRADE III  Cellular smears with abundant myxoid – chondroid stroma.  Mitotic figures present  Cells have single large cytoplasmic vacuoles displacing the nucleus to the periphery giving a signet- ring appearance.
  • 55. Mesenchymal chondrosarcoma  Aspirate – is gelatinous and blood tinged.  Cytological features 1. cellular , with rich myxoid chondroid background matrix. 2. Two cell populations – a small primitive appearing cells and cells showing chondrocytic differentiation. 3. Focal necrosis and acute inflammation 4. The chondrocyte like cell population with moderate to abundant cytoplasm containing vacuoles. 5. The cells characterized by eccentric nuclei with coarsely granular chromatin and distinct nucleoli.  Differential diagnosis – Small round cell malignancies , Intraosseous hemangiopericytoma.
  • 56. Mesenchymal chondrosarcoma  Clusters of small, round to oval tumor cells with sparse cytoplasm and irregular nuclei.  Cells embedded in a blue-violet collagenous matrix (MGG).
  • 57. Clear cell chondrosarcoma  Large epithelioid cells with abundant finely vacuolated cytoplasm,  a central or paracentral nucleus, fragments of cartilage, and  occasional osteoclast-like giant cells (MGG)
  • 58.
  • 59. GIANT CELL – CONTAINING LESIONS
  • 60. Case - 9  35 year old woman with h/o slow growing mass in left wrist since 1 year and pain since 4weeks.  X – ray showed – well defined osteolytic lesion with incomplete surrounding sclerosis with multiloculated appearance .
  • 62. Giant cell tumor  Cytological features  Hypercellular yield with both cohesive cell clusters and single cells.  Double-cell population: mononuclear spindle or round to ovoid cells and multinucleated osteoclast-like giant cells.  Mononuclear cells contain nuclei with open chromatin and prominent nucleoli.  The size of mononuclear cell nuclei is comparable to that in the osteoclast-like giant cells.  Classical pattern of smears includes giant cells attached to the periphery of clusters of mononuclear cells.  Absence of osteoid and cartilaginous matrix.
  • 63. Differential diagnosis  Aneurysmal bone cyst  Brown tumor of hyperparathyroidism  Reparative giant cell granuloma  Osteoblastoma  Giant cell-rich osteosarcoma
  • 64. Aneurysmal bone cyst  Multilocular, locally destructive lesion.  Age - < 20yrs.  Vertebral column, the craniofacial bones, and metaphysis of long tubular bones.  X- Ray - seen as osteolytic , expansile, eccentric lesions in metaphysis.
  • 65. ABC cytology  Cytologic features  Hemorrhagic aspirates  Variable numbers of multinucleated giant cells  Variable presence of clusters of spindled myofibroblastic cells  Histiocytes and inflammatory cells  Lack of significant cytologic atypia
  • 66. Brown Tumor of Hyperparathyroidism  X- Ray  Lytic lesion with irregular sclerosed cortex  Differential diagnosis and problems in diagnosis:  Conventional giant cell tumor  Aneurysmal bone cyst  Reparative giant cell granuloma
  • 67. Brown Tumor of Hyperparathyroidism  Cytologic features  Dispersed spindle cells or small- to medium-sized clusters of spindle cells  Osteoclast-like giant cells  Hemosiderin-laden macrophages
  • 68. Giant Cell Reparative Granuloma  X- Ray – Osteolytic ,eccentric lesion in the epiphysis without a sclerotic margin.  May show a soap bubble appearance.
  • 69. Giant Cell Reparative Granuloma  Cytologic features:  Sheets and clusters of spindle cells  Multinucleated giant cells  Osteoblasts  Histiocytes  ( a and b ) (MGG; H&E).  ( c ) Cell block - (H&E)
  • 70. VASCULAR LESIONS  Hemangioma – only blood is aspirated.  Strands of endothelial cells with spindled , bland nuclei may be found in smears .  Also seen are hemosiderin containing macrophages , osteoblasts and fibroblasts.
  • 71. Cystic lesions of bone  Unicameral bone cyst  Aneurysmal bone cyst  Telangiectatic Osteosarcoma  Intraosseous ganglion cyst  Subchondral Osteoarthritic Bone cyst  Intraosseous Epidermal cysts.
  • 72. BONE LESIONS COMPOSED OF SPINDLE – SHAPED CELLS
  • 73. Adamantinoma of long bones  2ND AND 6TH DECADE  M: f – 1.3 : 2  H/o dull aching pain with swelling.  X- Ray  Metaphysis / Diaphysis  Tibia / Fibula  Eccentric zone of lysis  Osteolytic area is bubbly / honeycomb
  • 74. On cytology  Cellular smears with small clusters of cells  Majority are spindle shaped, some are round to oval.  Distinct / absent cytoplasm  Necrotic debris in the background.
  • 75. Intraosseous desmoplastic fibroma  3rd decade.  Mandible , pelvic bones and femur.  Swelling , tenderness and aching pain.  X- ray – shows Lytic appearance with sclerotic margin.  Orthopantomograph well-defined radiolucent lesion over the right mandible
  • 76. Cytology  Spindle shaped cells in clusters .  Collagen fiber debris  Bland nucleus with fine chromatin and small indistinct nucleoli.  No mitotic figures seen.
  • 78. Case- 10  15 year old man with slow growing mass in the left arm since 1 year with redness and pain since 1 week.  X- RAY showed illdefined , permeative ,destructive intramedullary lesion .Onion skin appearance.
  • 79. Ewings sarcoma - cytology  Cellular  Neoplastic cells with uniform size and round shape  Bimodal population of – light & dark cells  Light cells – open chromatin  Dark cells – condensed chromatin  Glycogen / rosette like structures present  Scanty cytoplasm , appears as thin rim.
  • 80. Non – hodgkins lymphoma  Very rare  > 40 yrs  Male predominance  X- ray  Lytic appearance  Permeative moth eaten pattern  Cortex is lysed with extension into surrounding soft tissue.  Periosteal new bone formation – onion skin peal appearance.
  • 81. Cytology  Monorphous population of large lymphoid cells showing nuclear enlargement.  The background is dirty  Contains characteristic lymphoglandular bodies.  Atypical lymphocytes are 2- 3 times the size of small lymphocyte.
  • 82. Langerhans cell histiocytosis  5 – 15 YRS  3:2  Skull , jaw , humerus, rib , femur.  Metaphysis or diaphysis.  Benign.  X- ray  Lytic masses that may extend into soft tissue
  • 83. Cytology  cellular with large, polygonal cells with ample cytoplasm, nuclei are round, oval or bean shaped with fine and even chromatin and prominent longitudinal grooves Inconspicuous nucleoli, mild pleomorphism  No / minimal mitotic figures  Scattered eosinophils and neutrophils and multinucleated osteoclast-like giant cells  Necrosis common
  • 85. Breast carcinoma mets to bone  usually appear in the medullary cavity, spread to destroy the medullary bone, and then involve the cortex
  • 86. Cytology  Metastatic ductal carcinoma of the breast shows cells arranged in loose clusters. Inset. Details of nuclear morphology with coarse chromatin and prominent irregular nucleoli.
  • 87. Carcinoma prostate  densely sclerotic osteoblastic metastases, which frequently involve vertebral bodies and the pelvis  Metastatic foci can be obliterated by a pronounced osteoblastic reaction
  • 88. Cytology  . A,B. Large cohesive sheets of prostatic carcinoma cells.  the nuclei of the tumor cells are uniform in size with minimal atypia.  prominent nucleoli, and evenly distributed chromatin.
  • 89. Carcinoma of lung  O15 % of carcinomas metastases to bone  Lytic lesions in bone
  • 90. Cytology – mets of ca of lung  Clusters of the large lung adenocarcinoma cells showing obvious cytologic atypia
  • 91. Electron microscopy  Diagnosis of Langerhans cell histiocytosis (Birbeck granule)  Rare cases of osteosarcoma (osteoid)
  • 92. Cytochemistry  Alkaline phosphatase (ALP) – Osteoblastic differentiation  Positive in Osteosarcoma
  • 94. Algorithm of fnac of bony lesions
  • 95.
  • 96.
  • 98. Reporting the diagnosis on bone lesions  Sarcoma (histologic type of sarcoma or sarcoma not otherwise specified [NOS])  Benign tumor (histologic type or benign tumor NOS)  Metastasis (suggestion of primary or descriptive diagnosis)  Lymphohematologic malignancy (exact subtype defined or general classification as malignant lymphoma, non-Hodgkin lymphoma)  Non neoplastic lesion (infectious, reactive)  Non diagnostic (including insufficient) A standardized reporting of bone FNA has been suggested by Åkerman et al.
  • 99. To Summarize  Age , Clinical features, Specific site, Radiology , Clinical presentation and underlying conditions.  FNA technique should be based on the location of the tumor.  Algorithm approach helps in making a appropriate diagnosis.
  • 100.
  • 101.
  • 102. References  Cytopathology of bone and soft tissue tumors by Lester J Layfield  Current concepts in Bone and soft tissue tumors by Dr.Ajay Puri  Koss diagnostic cytology and its Histopathologic bases.  Atlas of Fine needle aspiration cytology by Henryk . A . Domanski.  Internet sources.

Editor's Notes

  1. They are uniform cells of rounded or triangular shape, with abundant cytoplasm, which often contains a clear “hof” area adjacent to the nucleus. The round nuclei with a central nucleolus are situated very close to the cytoplasmic membrane giving impression of almost protruding through it (H&E and MGG)
  2. Osteoclasts appear as scattered single large cells with abundant cytoplasm and multiple, uniform, round to oval nuclei. In (MGG)- a fine red cytoplasmic granulation is seen
  3. Composed of a hyaline matrix, which is reddish blue to violet with MGG or pink with (H&E). Normal chondrocytes present infrequently as a single cell
  4. Bone marrow cells. ( a and b ) Erythropoietic and myelopoietic cells and megakaryocytes appear occasionally in FNA smears from skeletal lesions. Megakaryocytes must not be misinterpreted as tumor cells (MGG)
  5. Neoplastic chondrocytes are round to oval with moderate to abundant cytoplasm with enlarged nuclei and moderately to coarsely granular chromatin and one to two dinstinct nucleoli. The cytoplasm may be vacuolated seen displacing the nucleus to the periphery of the cell.